Vorinostat in Treating Women With Ductal Carcinoma in Situ of the Breast

A Window Trial of Vorinostat in Patients With Ductal Carcinoma in Situ (DCIS) of the Breast

RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This clinical trial is studying how well vorinostat works in treating women with ductal carcinoma in situ of the breast.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Genetic: protein expression analysis; Other: laboratory biomarker analysis; Procedure: therapeutic conventional surgery; Procedure: neoadjuvant therapy; Other: immunohistochemistry staining method; Drug: vorinostat

Detailed Description

OBJECTIVES:

• To evaluate the in vivo molecular and biological effects of vorinostat by analyzing changes in proliferation and apoptosis, histone acetylation, and HDAC protein expression in women with ductal carcinoma in situ of the breast.

OUTLINE: Patients receive oral vorinostat twice a day for 3 days in the absence of unacceptable toxicity. Patients then undergo lumpectomy or mastectomy 2 hours after the last dose of vorinostat.

Blood and tissue samples are collected at baseline and during surgery for biomarker laboratory studies. Samples are analyzed by immunohistochemistry for Ki-67, HDAC1 and HDAC6 protein expression, and histone H4 and α-tubulin acetylation.

After completion of study therapy, patients are followed for 1 month and then every 6 months for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • UCSF Helen Diller Family Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed (by core biopsy) ductal carcinoma in situ

  • Stage 0 disease
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Menopausal status not specified
• ECOG performance status 0-2
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL
• Potassium and magnesium levels normal
• Prothrombin time or INR ≤ 1.5 times upper limit of normal (ULN) (unless the patient is receiving therapeutic anticoagulation)
• Partial thromboplastin time ≤ 1.2 times ULN (unless the patient is receiving therapeutic anticoagulation)
• Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 2 effective barrier methods of contraception
• No known psychiatric or substance abuse disorder that would preclude cooperation with the study requirements
• No active hepatitis A, B, or C infection
• No active HIV infection
• No other active infection
• No other malignancy within the past 5 years
• No condition that would interfere with the absorption or intake of vorinostat
• No history or current evidence of any condition or laboratory abnormality that would confound study results, interfere with the patient's participation in the full duration of the study, or that would not be in the best interest of the patient to participate

PRIOR CONCURRENT THERAPY:

• More than 2 weeks since prior IV antibiotics, antivirals, or antifungals
• No prior gastrointestinal surgery or other procedure that would interfere with the absorption or intake of vorinostat
• No prior or concurrent therapy with any other HDAC inhibitor, including valproic acid
• No prior treatment with any other investigational agent
• No concurrent systemic steroids
• No concurrent anticancer chemotherapy, radiotherapy, biological therapy, or other investigational therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vorinostat	Genetic: protein expression analysis; Other: laboratory biomarker analysis; Procedure: therapeutic conventional surgery; Procedure: neoadjuvant therapy; Other: immunohistochemistry staining method; Drug: vorinostat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Reduction in Ki-67 compared to baseline Ki-67	3 days prior to surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in HDAC1 and HDAC6 expression and histone H4 and α-tubulin acetylation in breast tissue and serum samples	3 days prior to surgery

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Laura Esserman, MD, MBA, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): November 3, 2011
• Study Completion (Actual): August 11, 2015

Study Registration Dates

• First Submitted: November 7, 2008
• First Submitted That Met QC Criteria: November 7, 2008
• First Posted (Estimate): November 10, 2008

Study Record Updates

• Last Update Posted (Actual): August 7, 2017
• Last Update Submitted That Met QC Criteria: August 4, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: ductal breast carcinoma in situ
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Breast Carcinoma In Situ; Carcinoma in Situ; Carcinoma; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Vorinostat
• Other Study ID Numbers: CDR0000617655; UCSF-077532; H10367-31833; UCSF-07031833